PUBLICATION

Behavioral screening for nightblindness mutants in zebrafish reveals three new loci that cause dominant photoreceptor cell degeneration

Authors
Maaswinkel, H., Riesbeck, L.E., Riley, M.E., Carr, A.L., Mullin, J.P., Nakamoto, A.T., and Li, L.
ID
ZDB-PUB-050603-10
Date
2005
Source
Mechanisms of ageing and development   126(10): 1079-1089 (Journal)
Registered Authors
Li, Lei, Maaswinkel, Hans
Keywords
Nightblindness, Degeneration, Mutation, Retina, Photoreceptor, Aging, Zebrafish
MeSH Terms
  • Animals
  • Behavior, Animal*
  • Neurodegenerative Diseases/genetics
  • Neurodegenerative Diseases/metabolism
  • Neurodegenerative Diseases/pathology
  • Night Blindness/genetics*
  • Night Blindness/metabolism
  • Night Blindness/pathology
  • Photoreceptor Cells, Vertebrate/metabolism*
  • Photoreceptor Cells, Vertebrate/pathology
  • Quantitative Trait Loci/genetics*
  • Zebrafish/genetics*
  • Zebrafish/metabolism
PubMed
15922406 Full text @ Mech. Ageing Dev.
Abstract
Here we report three dominant nightblindness mutations in zebrafish: nightblindness e (nbe), nightblindness f (nbf) and nightblindness g (nbg). The mutants were isolated in the F1 generation of N-ethyl-N-nitrosourea (ENU) mutagenized zebrafish using a behavioral assay based on visually mediated escape responses. Subsequently, electroretinographic (ERG) recordings were made, and histological sections were screened for degenerative processes. For each mutant line, correlation analysis between behavioral, ERG and histological parameters was performed, and their relationships were determined by either calculating the Pearson correlation coefficient or by ANOVA. nbe is characterized by severe rod outer segments (ROS) degeneration. The degeneration correlates weakly with behavioral threshold and ERG b-wave amplitude, however, behavioral threshold correlates strongly with ERG b-wave. nbf is characterized by a dual histological pathology: patchy ROS-degeneration and 'gaps' homogeneously distributed over the outer nuclei layer (ONL) and between cone outer segments (COS). The correlations between histological pathology and behavioral threshold, and between behavioral threshold and ERG b-wave amplitude are obvious, but the correlation between histology and b-wave amplitude is less prominent. nbg is characterized by moderate ROS degeneration and moderate correlation between histology and behavioral threshold. Interestingly, behavioral threshold correlated inversely with ERG b-wave amplitude and threshold. Thus, contrary to what is normally seen in other nightblindness mutants, in nbg, the fish with the lowest behavioral threshold had the smallest b-waves amplitudes and the highest b-wave threshold. In our interpretation, the major impairment in nbe is photoreceptor-specific. In nbf, both photoreceptor degeneration and altered post-photoreceptor signaling are responsible for the behavioral deficit. In nbg, we find hypersensitivity at a post-photoreceptoral level concurrently with behavioral impairment.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping